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bioRxiv · 10.1101/2022.05.24.493293

Drosophila Rif1 is critical for repair following P-element excision and influences pathway choice at double-strand breaks

Blanch, J. R.·Krishnamurthy, M.·Zuckerman, J. T.·McVey, M.
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Abstract

Rif1 plays important roles in the repair of DNA double-strand breaks in multiple organisms. In mammals, RIF1 promotes non-homologous end joining and suppresses homologous recombination by interacting with 53BP1 to inhibit resection. In Saccharomyces cerevisiae, Rif1 directly binds DNA to inhibit resection and promote non-homologous end-joining. Yeast Rif1 can also facilitate long-range resection and promote single-strand annealing. Since it is not clear if Rif1 regulates resection-mediated pathway choice in other eukaryotes, we explored the role of Rif1 in double-strand break repair in Drosophila melanogaster. We found that rif1 mutants are not sensitive to ionizing radiation or hydroxyurea, demonstrating that it is not essential for the resolution of DNA damage in Drosophila. However, we show that rif1 null mutants are largely unable to repair a specific type of double-strand break that is induced upon the excision of a P-element transposon. Furthermore, assessment of repair pathway choice at I-SceI-induced breaks revealed Rif1 suppresses homologous recombination and promotes single-strand annealing. Collectively, our findings illustrate Drosophila Rif1 shares functions with both its yeast and mammalian counterparts and serves a unique role in repairing P-element-induced double-strand breaks.

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Blanch, J. R., Krishnamurthy, M., Zuckerman, J. T., McVey, M.. 2022-05-25. Drosophila Rif1 is critical for repair following P-element excision and influences pathway choice at double-strand breaks. https://doi.org/10.1101/2022.05.24.493293

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